Ovarian cancer (a highly metastatic and lethal gynaecologic malignancy) is a challenging disease to treat, and since it presents with few early symptoms it is usually diagnosed late when in advanced stages, i.e. stage III (tumour on one or both ovaries with intraperitoneal metastasis) or stage IV (tumour on one or both ovaries with distant metastases to the lungs and liver) (Feldman, 1989; Friedlander, 1998; Seiden, 2001; Auersperg et al., 2001; Whitehouse and Solomons, 2003).
The current treatment for ovarian cancer makes use of aggressive cyto-reductive surgery, chemotherapy and external beam radiotherapy (Hoskins et al., 1994; MacGibbon et al., 1999; Trimble et al., 2003). Post-operatively, intravenous (IV) chemotherapy of a taxane (such as paclitaxel) or a platinum agent (such as carboplatin), or a combination thereof, is administered (Cannistra, 2004). The vasculature supplying tumour tissue is hyper-permeable and this renders intravascular therapy a preferred method for the delivery of anti-neoplastic agents (Maeda et al., 2000). The absence of effective lymphatic drainage from tumour tissue contributes in sustaining drug exposure to tumour tissues (Shama et al., 1996). However, due to the poor bioavailability of systemically administered anti-neoplastic drugs, chemo-resistant-tumours arise (Yusuf et al., 2003). Doxorubicin (Doxil®) and albumin-bound paclitaxel (Abraxane®) liposomes are approved by the FDA for potential use in treatment of solid tumours. However, their size (150 and 130 nm, respectively) limits their effectiveness in drug delivery (Unezaki et al., 1996; Dreher et al., 2006). Despite several studies having demonstrated the benefits of using intraperitoneal (IP) administration over intravenous administration (Alberts et al., 1996; Markman et al., 2001; Armstrong et al., 2006), the use of intraperitoneal chemotherapy to improve treatment in post-operative ovarian cancer patients has yielded controversial clinical outcomes that discourage its use as a treatment option compared to intravenous chemotherapy (Dubbelman et al., 1988; Markman et al., 1992; Markman and Walker, 2006; Ozols et al., 2006; Swart et al., 2008).
Patients suffering from recurrent ovarian cancer undergo extensive chemotherapy, radiotherapy or a combination of the two as no effective curative therapy is currently available (Jacobs et al., 1992; Menon and Jacobs, 2002).
There is therefore a need for new compositions or methods for treating ovarian and related cancers which avoid at least some of the problems described above or which reduce chemoresistance or limit the rapid metastatic spread (intraperitoneally and distant) of ovarian cancer cells.